The objectives of the projects outlined in this shared equipment application are broadly defined to provide small-scale mechanical testing data for a large group of NIH-sponsored investigators with expertise in areas of biomaterials development for tissue engineering applications, analysis of tissue repair and regeneration, and molecular studies of bone and joint tissue disorders. The long-term aims are: Aim 1: Establish expertise in nanomechanical testing within the UCHC Micromechanics Core Faciltiy as an additional service to UCHC and regional investigators. Aim 2: Educate and train investigators to use nanomechanical test instruments, with additional focus on investigators in discplines outside of physics and engineering (i.e., biologists). Aim 3: Provide nanomechanical testing on a fee-for-service basis, utilizing the management and operational model of our well-established Micro-CT Imaging &Micromechanics core facility. Aim 4: Disseminate findings and new techniques through publication and presentation of results to national and international audiences. Nanomechanical testing will be used: 1) to measure properties of biomaterials and coatings at minute length scales, allowing direct tests of tissue engineering scaffolds with characteristic dimensions as small as micrometers or tens of nanometers. This will allow initial characterization of material integrity to test hypotheses for improving material behavior toward that of biological extracellular matrix;2) to examine the integrity of repair and regenerative tissues, including tissue-biomaterial interfaces;3) for phenotypic mechanical property measurement of bone, tooth, cartilage, and other soft tissue structures obtained from mice with unique genetic manipulations useful for studying human disease processes;4) to develop novel laboratory benchtop tests to improve existing assays, such as scratch-fracture tests of murine joint cartilage and the optical profilometry approach we describe in the application for measuring volumetric bone resorption rates in osteoclast cell cultures. Collectively, these methods provide a regimented solution to mechanical surface testing of small length scale constructs associated with animal tissues, tissue engineering development, and tissue repair in small animal models. The data provided by nanometer and micrometer scale mechanical tests is paramount in these studies, allowing for meaningful acquisition and interpretation of pre-clinical data in studies aimed at treating musculoskeletal tissue injuries and disorders.